药名：Caprelsa(凡德他尼vandetanib)

适应症：转移性甲状腺髓样癌

获批日期：4月6日

类型：小分子药物

简介：阿斯利康的这个抗癌药物在美国和欧盟都获得了监管部门的批准。欧盟人用医药产品委员会(CHMP)推荐欧盟批准Caprelsa，而美国也在去年春季批准了这个药物。，这种新药是一种口服的激酶抑制剂，是第一个获批的治疗甲状腺髓样癌（medullary thyroid cancer，MTC）的有效的药物。

制造商：
阿斯利康制药

类药物：
激酶抑制剂。

活性成分（S）：
凡德他尼100毫克，300毫克，制表符。

指示（S）：
不能手术切除的局部晚期或转移性疾病患者的症状或甲状腺髓样癌。

药理学：
凡德他尼抑制酪氨酸激酶的活动，包括那些与表皮生长因子受体，血管内皮细胞生长因子受体和酪氨酸蛋白激酶6相关。它已被证明能够抑​​制内皮细胞迁移，增殖，存活，并在体外血管生成，抑制酪氨酸激酶磷酸化。凡德他尼降低肿瘤细胞诱导的血管生成，肿瘤血管通透性，并抑制在体内的肿瘤生长和转移的小鼠模型。

临床试验：
一个双盲对照研究，涉及331例不能手术切除的局部晚期或甲状腺髓样癌进行了评估凡德他尼与安慰剂无进展生存的改善。还审议了总生存率和整体客观反应率。一个显着改善，到凡德他尼的患者的无进展生存证明。的无进展生存期的主要分析时间，15％的患者已经死亡，并在两个治疗组之间的总生存期没有显着差异。整体客观反应率是44％者给予凡德他尼相比，安慰剂组为1％;所有的客观回应部分反应。

法律分类：
接收

成人：
请勿挤压选项卡。为口头或NGT组管理的非碳酸水可分散2盎司的标签，避免接触皮肤，粘膜的分散。 300毫克，每日一次。肾功能损害（肌酐清除率<50mL/min）：最初为200mg，每日一次。如果发生严重的毒性或QTc间期延长（见文献）减少剂量。不要错过的剂量范围内采取的下一个剂量的12小时。

儿童：
不推荐。

禁忌（S）：
先天性长QT综合征。

警告/注意事项：
低钙血症，低钾血症，低镁血症，QTcF的时间间隔> 450msec，尖端扭转型，缓慢性心律失常的历史，无偿心脏衰竭，近期咯血：不推荐。室性心律失常。近期心肌梗死。监视器电解质（尤其是钾离子，钙+，镁+），促甲状腺激素，和心电图QT间期延长在基线，2-4周和8-12周开始，然后每隔3个月后，和剂量减少或剂量中断后2周;减少如需要剂量。开始前纠正电解质紊乱。维护血清K +至少4mEq/mL。肝功能不全（Child - Pugh分级B或C）：不推荐。暂停治疗和后续如果发生呼吸困难，咳嗽，发烧，QTcF> 500毫秒，或后部白质脑病症状（RPLS）。避免阳光，紫外线光。老人。 （Cat.D）（可能对胎儿造成伤害，使用4个月期间和停药后的适当，有效的避孕）怀孕，哺乳期的母亲：不建议。

相互作用（S）：
避免强CYP3A4诱导剂（如卡马西平，地塞米松，苯妥英，苯巴比妥，利福平，利福布丁，利福喷丁，圣约翰的草）。避免使用其他药物，可以延长QT间隔（例如，胺碘酮，丙吡胺，普鲁卡因胺，索他洛尔，多非利特，氯喹，克拉霉素，多拉司琼，格拉司琼，氟哌啶醇，匹莫齐特，美沙酮，莫西沙星）。

不良反应（S）：
（如果严重的中止）腹泻，皮疹，痤疮，恶心，高血压，头痛，乏力，食欲减退，腹痛，钙或葡萄糖下降，增加了ALT，QT间期延长，尖端扭转型，突然死亡，严重的皮肤反应（例如，史蒂文斯约翰逊综合征停止，如果发生），间质性肺疾病，缺血性脑血管事件，出血，心力衰竭，甲状腺功能减退，高血压危象，RPLS。

注：
处方和药房必须参加Caprelsa REMS计划通过致电（800）236-9933或访问www.caprelsarems.com。

如何提供：
标签30

最后更新：
2011年8月3日

The European Commission has approved AstraZeneca’s thyroid cancer pill Caprelsa.
Caprelsa (vandetanib) is now available in Europe for the treatment of aggressive and symptomatic medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Advanced medullary thyroid cancer (MTC) is a rare type of the disease with a poor prognosis, and currently there are no approved therapies in Europe.

But whilst the drug was approved, there was one snag: Caprelsa may not be as beneficial in patients without, or are not known to have, a particular mutation - the Rearranged during Transfection (RET) mutation.

For patients in whom RET mutation is not known or is negative, a possible lower benefit should be taken into account before treatment, AZ said.

The firm added that its clinical data shows patients benefit from treatment with the drug regardless of their RET status.

But in line with Europe’s requirements, AZ said it would conduct a further study to confirm the benefits in patients who are RET-negative.

A pharmacovigilance plan for Caprelsa will also be implemented as part of the marketing authorisation, given its high number of common adverse events.

Caprelsa works as a once-daily oral treatment that uses two distinctive mechanisms of action.

The first is by blocking the blood supply to the tumour, by slowing the vascular endothelial growth factor receptor pathway and reducing the growth and survival of the tumour through epidermal growth factor receptor and RET pathways.
 CAPRELSA

Indication(s):

Symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Pharmacology:

Vandetanib inhibits the activity of tyrosine kinases, including those associated with epidermal growth factor receptor, vascular endothelial cell growth factor receptor, and protein tyrosine kinase 6. It has been shown to inhibit endothelial cell migration, proliferation, survival, and angiogenesis in vitro, and it inhibits the phosphorylation of tyrosine kinase. Vandetanib reduces tumor cell-induced angiogenesis, tumor vessel permeability, and inhibits tumor growth and metastasis in vivo in murine models.

Clinical Trials:

A double-blind study involving 331 patients with unresectable locally advanced or medullary thyroid cancer was conducted to evaluate improvement in progression-free survival for vandetanib versus placebo. Overall survival and overall objective response rate were also examined. A statistically significant improvement in progression-free survival for patients randomized to vandetanib was demonstrated. At the time of primary analysis of progression-free survival, 15% of the patients had died, and there was no significant difference in overall survival between the two treatment groups. The overall objective response rate was 44% for those given vandetanib compared to 1% for placebo; all of the objective responses were partial responses.

Legal Classification:

Rx

Adults:

Do not crush tabs. May disperse tabs in 2 ounces noncarbonated water for oral or NGT administration; avoid contact of dispersion with skin, mucous membranes. 300mg once daily. Renal impairment (CrCl<50mL/min): initially 200mg once daily. Reduce dose if severe toxicity or QTc interval prolongation occurs (see literature). Do not take a missed dose within 12hrs of the next dose.

Children:

Not recommended.

Contraindication(s):

Congenital long QT syndrome.

Warnings/Precautions:

Hypocalcemia, hypokalemia, hypomagnesemia, QTcF interval >450msec, history of torsades de pointes, bradyarrhythmias, uncompensated heart failure, recent hemoptysis: not recommended. Ventricular arrhythmias. Recent MI. Monitor electrolytes (esp. K⁺, Ca⁺⁺, Mg⁺⁺), TSH, and ECG for QT prolongation at baseline, 2–4 weeks and 8–12 weeks after starting, then every 3 months, and after dose reductions or dose interruptions >2weeks; reduce dose as needed. Correct electrolyte disturbances before starting. Maintain serum K⁺ at least 4mEq/mL. Hepatic impairment (Child-Pugh B or C): not recommended. Suspend therapy and follow-up if dyspnea, cough, fever, QTcF >500msec, or posterior leukoencephalopathy symptoms (RPLS) occur. Avoid sun, UV light. Elderly. Pregnancy (Cat.D) (may cause fetal harm; use appropriate effective contraception during and for 4 months after stopping therapy), nursing mothers: not recommended.

Interaction(s):

Avoid strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampin, rifabutin, rifapentine, St.John’s Wort). Avoid other drugs that can prolong QT interval (eg, amiodarone, disopyramide, procainamide, sotalol, dofetilide, chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, pimozide, methadone, moxifloxacin).

Adverse Reaction(s):

Diarrhea (suspend if severe), rash, acne, nausea, hypertension, headache, fatigue, decreased appetite, abdominal pain, decreased calcium or glucose, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg, Stevens-Johnson syndrome; discontinue if occurs), interstitial lung disease, ischemic cerebrovascular events, hemorrhage, heart failure, hypothyroidism, hypertensive crisis, RPLS.

Notes:

Prescribers and pharmacies must enroll in the Caprelsa REMS program by calling (800) 236-9933 or visit www.caprelsarems.com.

How Supplied:

Tabs—30

Last Updated:

8/3/2011
---------------------------------------------------------------
原产地英文商品名:
VANDETANIB 100mg/tab 30tabs/bottle
原产地英文药品名:
VANDETANIB
中文参考商品译名:
凡德他尼 100毫克/片 30片/瓶
中文参考药品译名:
凡德他尼
生产厂家中文参考译名:
IPR PHARMS INC
生产厂家英文名:
IPR PHARMS INC

---------------------------------------------------------------
原产地英文商品名:
VANDETANIB 300mg/tab 30tabs/bottle
原产地英文药品名:
VANDETANIB
中文参考商品译名:
凡德他尼 300毫克/片 30片/瓶
中文参考药品译名:
凡德他尼
生产厂家中文参考译名:
IPR PHARMS INC
生产厂家英文名:
IPR PHARMS INC